Trombocytopenia: One of the Markers of Disseminated Intravascular Coagulation

Cate, Hugo Ten

doi:10.1159/000083838

Cited by 29 publications

(10 citation statements)

References 11 publications

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“…Dependent on the cause of thrombocytopenia, MP might be helpful in restoring haemostasis and prevention of overt bleeding in patients after surgery or liver biopsy (in case of severe liver cirrhosis). On the other hand, the current study provides a rationale for the hesitation on prophylactic transfusion of platelet concentrates in disseminated intravascular coagulation (DIC) patients, despite their low platelet counts (Rebulla, 2001; ten Cate, 2004). The presence of procoagulant MP in platelet concentrates could enhance systemic coagulation in these patients and maintain the pathogenic loop sustaining DIC.…”

Section: Discussionmentioning

confidence: 97%

Effects of storage‐induced platelet microparticles on the initiation and propagation phase of blood coagulation

et al. 2006

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Summary Platelets shed microparticles, which support haemostasis via adherence to the damaged vasculature and by promoting blood coagulation. We investigated mechanisms through which storage‐induced microparticles might support blood coagulation. Flow cytometry was used to determine microparticle number, cellular origin and surface expression of tissue factor (TF), procoagulant phosphatidylserine (PtdSer) and glycoprotein (GP) Ib‐α. The influence of microparticles on initiation and propagation of coagulation were examined in activated factor X (factor Xa; FXa) and thrombin generation assays and compared with that of synthetic phospholipids. About 75% of microparticles were platelet derived and their number significantly increased during storage of platelet concentrates. About 10% of the microparticles expressed functionally active TF, as measured in a FXa generation assay. However, TF‐driven thrombin generation was only found in plasma in which tissue factor pathway inhibitor (TFPI) was neutralised, suggesting that microparticle‐associated TF in platelet concentrates is of minor importance. Furthermore, 60% of all microparticles expressed PtdSer. In comparison with synthetic procoagulant phospholipids, the maximal rate of thrombin formation in TF‐activated plasma was 15‐fold higher when platelet‐free plasma was titrated with microparticles. This difference could be attributed to the ability of microparticles to propagate thrombin generation by thrombin‐activated FXI. Collectively, our findings indicate a role of microparticles in supporting haemostasis by enhancement of the propagation phase of blood coagulation.

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Section: Discussionmentioning

confidence: 97%

Effects of storage‐induced platelet microparticles on the initiation and propagation phase of blood coagulation

et al. 2006

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“…The ISTH overt DIC criteria use global markers, such as prothrombin time (PT) and platelet count for scoring. The coagulation factors and platelets are consumed and decrease over time because of progressive thrombin generation and endothelial injury, thus it takes several days to reveal their abnormalities and fulfill the overt DIC criteria in the course of sepsis [9,10]. Furthermore, introduction of the concept of pre-DIC, which is considered as the stage prior to overt DIC, has failed to predict disease progression.…”

Section: Introductionmentioning

confidence: 99%

Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study

et al. 2014

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IntroductionCurrent criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis.MethodsA single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α2-plasmin inhibitor (PI), plasmin-α2-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days.ResultsA total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively).ConclusionsSevere coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.

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“…Among platelet-suppressive manifestations, thrombocytopenia commonly develops in anthrax patients and animal models [8], [14], [16]. Thrombocytopenia can be caused by two main reasons: a reduced production of platelets by the progenitor megakaryocytes [17], and an increased platelet loss by rapid consumption [18]. Previous studies have shown that PA binds to anthrax receptors in all lineages of hematopoietic progenitors in the bone marrow, including platelet precursor megakaryocytes [19], however, megakaryopoiesis suppression by LT has not been specifically characterized.…”

Section: Introductionmentioning

confidence: 99%

Suppressive Effects of Anthrax Lethal Toxin on Megakaryopoiesis

et al. 2013

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Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis. LT challenge suppresses platelet counts and platelet function in mice, however, the mechanism responsible for thrombocytopenia remains unclear. LT inhibits cellular mitogen-activated protein kinases (MAPKs), which are vital pathways responsible for cell survival, differentiation, and maturation. One of the MAPKs, the MEK1/2-extracellular signal-regulated kinase pathway, is particularly important in megakaryopoiesis. This study evaluates the hypothesis that LT may suppress the progenitor cells of platelets, thereby inducing thrombocytopenic responses. Using cord blood-derived CD34+ cells and mouse bone marrow mononuclear cells to perform in vitro differentiation, this work shows that LT suppresses megakaryopoiesis by reducing the survival of megakaryocytes. Thrombopoietin treatments can reduce thrombocytopenia, megakaryocytic suppression, and the quick onset of lethality in LT-challenged mice. These results suggest that megakaryocytic suppression is one of the mechanisms by which LT induces thrombocytopenia. These findings may provide new insights for developing feasible approaches against anthrax.

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Trombocytopenia: One of the Markers of Disseminated Intravascular Coagulation

Cited by 29 publications

References 11 publications

Effects of storage‐induced platelet microparticles on the initiation and propagation phase of blood coagulation

Effects of storage‐induced platelet microparticles on the initiation and propagation phase of blood coagulation

Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study

Suppressive Effects of Anthrax Lethal Toxin on Megakaryopoiesis

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